The objectives of this three phase crossover PK/PD study of an open label design for phase one and two, and a double-blind, randomized design for phase three were as follows: 1) To characterize the pharmacokinetic profile of three hydromorphone formulations - Intravenous (IV), oral immediate release (IR), and new oral slow release (SR). 2) To test for the linearity of the pharmacokinetic profile of three geometrically increasing doses of the novel SR formulation. 3) To characterize the PK/PD relationship of IV hydromorphone for an EEG effect measure. 4) To characterize the PK/PD relationship of IR and SR hydromorphone for an analgesic effect measure. 5) To characterize the PK/PD relationship of SR hydromorphone for a subjective opioid effect measure. Twelve normal, healthy subjects (6 male and 6 female) participated and completed the study. The six study periods were separated by at least 7 days and consisted of a 24-h period for IV administration, a 24-h period for administration of IR-hydromorphone, and 4 periods each lasting 38-h for administration of 3 different doses of SR-hydromorphone and placebo, respectively. The pharmacokinetics were assessed by measuring serial arterial and venous hydromorphone concentrations. Compartment and non-compartmental analysis of the pharmacokinetics was performed. EEG was recorded for 6 hours after IV administration of hydromorphone. Experimental pain models were employed for 6 and 30 hours after oral administration of IR and SR hydromorphone, respectively, to quantify the analgesic efficacy. Side effects and effects on mood and mental condition were assessed with a brief, subjective opioid effects questionnaire.